Delivering material to a patient

ABSTRACT

A delivery catheter for delivering material(s) into the body of a mammal can include a first elongated member and a second elongated member. At least a portion of the second elongated member can be slidably disposed within a lumen of the first elongated member. The delivery catheter can mix two materials and then introduce the mixed materials into the body of a mammal.

TECHNICAL FIELD

This invention generally relates to medical devices and methods fordelivering material(s) to a patient.

BACKGROUND INFORMATION

Medical conditions sometimes require the replacement or support of adamaged tissue or structure. Such replacement or support can be made viathe use of fillers, either temporarily or permanently. Exemplaryapplications of such filler compositions include sutures and surgicalnets that have been used for organ support in spleen, liver, and kidneyrepair procedures. A non-immunogenic, bioerodible, implantablecomposition with alginate fibers is known, as is a biological tissuetransplant coated with a stabilized multi-layer alginate. Transplantableartificial pancreatic tissue can be prepared from an alginic acid gelprecursor, a matrix monomer, and pancreas cells with Ca²⁺ ions and amatrix monomer polymerization catalyst. The calciumalginic acidcomposition is used to provide mechanical integrity to the mixture whilethe matrix monomer is polymerized, after which the calcium-alginic acidcomposition is removed to leave a porous matrix. The calcium-alginicacid composition functions as a processing aid not as a structuralmember in the final artificial device. Also, alginate fibers have beenused in preparation of wound dressings.

Formation of fibers with ionically crosslinked alginates requirescontacting crosslinking agents, such as the cation of choice, with thealginate of choice. While contacting a crosslinking agent with analginate generally is not considered difficult, controlling theformation and termination of the alginate fibers has been difficult. Thedifficulty arises from the rapidity in which alginate crosslinks onceexposed to crosslinking ions. Controlling fiber formation and fibertermination is a major problem of existing preparation methods thatemploy the simple mixing of the two agents.

SUMMARY OF THE INVENTION

Because of the rapid rate of crosslinking, an alginate and acrosslinking agent generally should be separately delivered to, andcrosslinked at, the location in need of alginate fibers. Such in situformation provides maximum effectiveness in generating alginate fiberswith the desired shape and size at the desired location. Introductionand/or relocation of formed alginate fibers generally is not effectiveor efficient.

One object of the invention involves mixing, delivering, and terminatingdelivery of a crosslinking agent and a crosslinkable polymer at thelocation of need, thereby providing efficient delivery of fibrousmaterial and minimizing potential for complications.

In one aspect, the invention relates to a delivery catheter. Thedelivery catheter can include a first elongated member and a secondelongated member. The first elongated member defines a first distalopening, a first lumen extending within the first elongated member, anda distal section of the first lumen near the first distal opening. Thefirst elongated member delivers a first material through the first lumenand into the distal section of the first lumen. The second elongatedmember includes a distal valve and defines a second lumen extendingwithin the second elongated member. The second elongated member isdesigned for delivering a second material through the second lumen andthe distal valve into the distal section of the first lumen. At least aportion of the second elongated member is slidably disposed within atleast a portion of the first lumen such that the distal valve isselectively slidable (i) to allow delivery of the second materialthrough the second lumen, the distal valve, and into the distal sectionof the first lumen, and (ii) to push at least some of the first andsecond materials from the distal section of the first lumen out of thefirst distal opening.

In one embodiment of the invention, the delivery catheter comprises aone-way flowcontrol distal valve such as a slit in the wall of the innerelongated member that opens and closes upon pressure differential. Inanother embodiment, the delivery catheter further contains an accessjoint for insertion of at least a portion of the second elongated memberinto a portion of the first lumen. In yet another embodiment, thedelivery catheter further contains a first and second pumps connected tothe first and second elongated members. Each of the pumps may furthercontain an injector. In yet another embodiment, the delivery cathetercomprises a stabilizing structure (e.g. spokes) to stabilize the secondelongated member so that it is substantially coaxial to the firstelongated member. In yet another embodiment, the first elongated memberof the catheter is transmutable such that the distal valve is locatableoutside the first lumen and outside the first distal opening.

In another aspect, the invention relates to a method for delivering anextrudable material within the body of a mammal. The method includes thefollowing steps. A delivery catheter as described above is provided todeliver a first and second materials into a body. A fibrous material isextruded out of the distal section and into the body of a mammal. In oneembodiment, the extrusion step includes delivering through the firstlumen to the distal section a first material having a crosslinking agentand delivering through the second lumen to the distal section a secondmaterial having a crosslinkable polymer. In one embodiment, the firstmaterial surrounds the second material as both materials are introducedinto the distal section of the first lumen. The contacting of the firstmaterial with the second material results in the formation ofcrosslinked polymeric material and the generation of a fiber inside thedistal section. The sustained delivery of the first and second materialsinto the distal section forces the fiber to be extruded out of thedistal section into a body when the catheter is positioned within a bodyof a patient. The formation of the crosslinked polymeric material may bestopped by terminating the feed of either or both of the first andsecond materials into the distal section. The method may further includecutting the crosslinked polymeric material so formed. To cut thepolymeric material, introduction of one or both of the first and secondmaterials can be terminated. The crosslinked polymeric material can becut by the distal valve. To facilitate its exit, the crosslinkedpolymeric material can be pushed by a pressure exerted from the distalvalve and/or by the pressure exerted from the sustained delivery solelyof the first material into and out of the distal section.

The foregoing and other aspects, features, embodiments, and advantagesof the invention will become apparent from the following description,figures, and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings are not necessarily to scale, emphasis instead generallybeing placed upon illustrating the principles of the invention.

FIG. 1 is a cross-sectional schematic view of a distal portion of onepossible embodiment of a delivery catheter according to the invention.

FIG. 2a is a partial cross-sectional schematic view of an embodiment ofan entire delivery catheter according to the invention.

FIG. 2b is a cross-sectional view of a possible embodiment of aninjector of the delivery catheter according to the invention.

FIG. 2c is a cross-sectional view of a possible embodiment of aninjector of the delivery catheter according to the invention.

FIG. 3 is a cross-sectional schematic view of the second elongatedmember of one possible embodiment of a delivery catheter according tothe invention.

FIG. 4a shows a schematic front view of a closed deformable flow-controlvalve of one possible embodiment of a delivery catheter according to theinvention.

FIG. 4b shows a schematic side view of a closed deformable flow-controlvalve of one possible embodiment of a delivery catheter according to theinvention.

FIG. 4c shows a schematic front view of an opened deformableflow-control valve of one possible embodiment of a delivery catheteraccording to the invention.

FIG. 4d shows a schematic side view of an opened deformable flow-controlvalve of one possible embodiment of a delivery catheter according to theinvention.

FIG. 5a shows a schematic perspective view of a closed deformableflow-control valve of one possible embodiment of a delivery catheteraccording to the invention.

FIG. 5b shows a schematic side view of a closed deformable flow-controlvalve of one possible embodiment of a delivery catheter according to theinvention.

FIG. 5c shows a schematic perspective view of an opened deformableflow-control valve of one possible embodiment of a delivery catheteraccording to the invention.

FIG. 5d shows a schematic side view of an opened deformable flow-controlvalve of one possible embodiment of a delivery catheter according to theinvention.

FIG. 6a shows a schematic perspective view of a closed deformableflow-control valve of one possible embodiment of a delivery catheteraccording to the invention.

FIG. 6b shows a schematic side view of a closed deformable flow-controlvalve of one possible embodiment of a delivery catheter according to theinvention.

FIG. 6c shows a schematic perspective view of an opened deformableflow-control valve of one possible embodiment of a delivery catheteraccording to the invention.

FIG. 6d shows a schematic side view of an opened deformable flow-controlvalve of one possible embodiment of a delivery catheter according to theinvention.

FIG. 7a shows a schematic perspective view of a closed deformableflow-control valve of one possible embodiment of a delivery catheteraccording to the invention.

FIG. 7b shows a schematic side view of a closed deformable flow-controlvalve of one possible embodiment of a delivery catheter according to theinvention.

FIG. 7c shows a schematic front view of an opened deformableflow-control valve of one possible embodiment of a delivery catheteraccording to the invention.

FIG. 7d shows a schematic side view of an opened deformable flow-controlvalve of one possible embodiment of a delivery catheter according to theinvention.

FIG. 8a shows a cross-sectional schematic view of a Y-shaped jointportion of a delivery catheter according to the invention.

FIG. 8b shows a cross-sectional schematic view of a T-shaped jointportion of a delivery catheter according to the invention.

FIG. 9a shows a partial cross-sectional schematic view, illustrating onepossible position of the second elongated member within the lumen of thefirst elongated member.

FIG. 9b shows a partial cross-sectional schematic view, illustrating onepossible position of the second elongated member within the lumen of thefirst elongated member.

FIG. 9c shows a partial cross-sectional schematic view, illustrating onepossible position of the second elongated member within the lumen of thefirst elongated member.

FIG. 10a is a schematic view of a possible embodiment of a deliverysystem according to the invention.

FIG. 10b is a transversal cross-sectional view of a distal portion ofthe delivery system shown in FIG. 10a, illustrating the positioning ofthe first and second elongated members.

FIG. 11a is a schematic view of an embodiment of a delivery catheteraccording to the invention, illustrating an embodiment of a gun-likedelivery system according to the invention.

FIG. 11b is a transversal cross-sectional view of a distal portion ofthe delivery system shown in FIG. 10a, illustrating the positioning ofthe first and second elongated members.

FIG. 11c is a longitudinal cross-sectional view of a distal portion ofthe delivery system shown in FIG. 10a, illustrating the distal sectionof the first lumen.

FIG. 12 is a partial cross-sectional schematic view of an embodiment ofa delivery catheter according to the invention, illustrating thearrangement of an embodiment of a delivery system according to theinvention including three elongated members (parallel/coaxialarrangement).

FIG. 13 is a partial cross-sectional schematic view of an embodiment ofa delivery catheter according to the invention, illustrating thearrangement of an embodiment of a delivering system according to theinvention including three elongated members (all-coaxial arrangement).

FIG. 14a shows formation of fibrous material within a deliveringcatheter according to the invention.

FIG. 14b shows removal of fibrous material from a delivery catheteraccording to the invention.

DESCRIPTION

The invention generally relates to delivery catheters and relatedmethods for delivering and mixing agents within the body of a patient.Referring to FIG. 1, in one embodiment, a delivery catheter 10 includesa first elongated member 100 and a second elongated member 200. Thefirst elongated member 100 defines a first distal opening 110 and afirst lumen 120 extending within the first elongated member 100. Thefirst elongated member 100 conveys a first material through the firstlumen 120 and into a distal section 140 of the first lumen 120 near thefirst distal opening 110. The second elongated member 200 includes adistal valve 210 and a second lumen 220 extending within the secondelongated member 200. The second elongated member 200 conveys a secondmaterial through the second lumen 220 and the distal valve 210 and intothe distal section 140. At least a portion of the second elongatedmember 200 is slidably disposed within at least a portion of the firstlumen 100 such that the distal valve 210 is selectively slidable (i) toallow delivery of the second material through both the second lumen 220and the distal valve 210 and into the distal section 140, and (ii) topush at least some of the first and second materials and the fiberresulting from their mixing from the distal section 140 and out of thefirst distal opening 110.

The distal valve 210 may be a flow-control valve placed at the distalend of the second elongated member 200. The distal valve may be used tocontrol the flow of the first and second materials and the formation offibers resulting from crosslinking of the second material (such as analginate solution) with the first material (such as a calcium chloridesolution).

Now referring to FIG. 2a, the delivery catheter 12 further includes aY-shaped access joint or seal 160 which permits access by the distal endof elongated member 200 to the first lumen 120. In addition, thedelivery catheter 12 includes a first injector 180, a second injector280, and connection ports or seals 170 and 270 which connect injectors180 and 280 with the first and second elongated members 100 and 200,respectively. The first and second injectors 180 and 280 are used fordelivering agents to the distal section 140 through the first and secondelongated members 100 and 200.

Any device may be used as an injector as long as the desired purpose isachieved. For example, the injector may be a syringe as shown in FIG.2b. The syringe includes tubular walls 182 which define a syringereservoir 186, a shaft 184, a handle 188, and a seal 187. Alternativelyas shown in FIG. 2c, an injector 171 includes a reservoir 172 connectedto the rest of the delivery catheter 12 through a tube 174 and a valve176 to control fluid flow. The rate of flow can also be adjusted bychanging the height of the reservoir 172 relative to the valve 176.Injectors may incorporate measurement grades thereon to measure theamount of delivery from each injector.

The second elongated member 200 may have a constant outer diameterthroughout its length or it may have a narrowing or widening portion.Referring to FIG. 3, one embodiment of the second elongated member 200of the delivery catheter includes a wider proximal portion 204 and anarrower distal portion 206. A distal valve 210 is located in the distalportion 206 of the second elongated member 200. The second elongatedmember 200 defines a lumen or passageway 220. The distal valve 210 maybe a one-way flow-control valve designed to allow liquid or gel to flowout of the second lumen 220 through the distal valve 210 but not backinto the second lumen 220. The distal valve 210 may also be a two-wayflow control valve if the application so requires.

The distal valve 210 may include a deformable slit 214 cut in the walls212 forming the distal end of the second elongated member 200. Thedistal valve 210 operates by a deformation of the walls 212 adjoiningthe slit 214 upon application of greater pressure in the second lumen220 than in the distal section 140. This pressure differential may beapplied either by increasing pressure in the second lumen 220 or bydecreasing pressure in the distal section 140. Upon a pressuredifferential, portions of the walls 212 of the distal valve 210 movedistally and radially outwards raising the top lip and/or lowering thelower lip of the slit 214 and thus creating an opening. Upon a negativepressure differential, the walls 212 of the distal valve 210 press thetop lip downwards and/or the bottom lip upwards until the lips abut oneanother. This abutting of the lips and the curvature and strength of thewalls 212 in distal valve 210 prevent the walls 212 from collapsinginwards and thus resist the negative pressure differential fromreopening the valve and liquid to flow in the opposite direction, backinto the second lumen 220. Thus, operation of the distal valve 210 maybe controlled by varying the pressure inside the second lumen 220. Thedeformable slit can be of many shapes and sizes depending on theapplications. Illustrative examples are shown in FIGS. 4a-d, 5 a-d, 6a-d, and 7 a-d.

FIGS. 4a-b show one embodiment of the distal valve having a transversalslit 214 in a closed configuration. The deformable slit 214 is a linearcut in a rounded tip of the second elongated member 200. When open(FIGS. 4c-d) the lips of distal valve defines an eye-shape opening 216.Depending on the flexibility of the material forming the secondelongated member, the opening geometry may vary from a three-legged starto a triangle or a four-legged star to a square, for examples. In FIGS.5a-b, the deformable slit 214 has three arms of equal length separatedby three pie-shape walls (three 120° angles). Upon positive pressuredifferential, the three walls deform distally to form a three-leggedstar opening 216 (FIGS. 5c-d). In FIGS. 6a-b, the deformable slit 214and the corresponding opening 216 have four arms of equal lengthseparated by four pie-shape walls (four 90° angles). Upon positivepressure differential, the four walls deform distally to form afour-legged star opening 216 (FIGS. 6c-d). In FIGS. 7a-b, the deformableslit 214 is “C”-shaped walls that opens to form a “D”-shaped opening 216(FIGS. 7c-d).

When open, the slit openings can have an area from about 0.00001 mm² toabout 100 mm² depending on the applications and the desiredcross-section size of the resulting fibers. For example, maximum openingarea may range from about 0.00001 mm² to about 0.0001 mm², from about0.0001 mm² to about 0.001 mm², from about 0.001 mm² to about 0.01 mm²,from about 0.01 mm² to about 0.1 mm², from about 0.1 mm² to about 1 mm²,from about 1 mm² to about 10 mm², and from about 10 mm² to about 100mm². The distal valve 210 may be a built-in feature at the distal end ofthe distal portion 206 of the second elongated member 200. Thus, in oneembodiment, the deformable slit 214 is created on the distal tip of thesecond elongated member 200. Alternatively, the distal valve 210 may bea separate device attached (such as by screwing or direct bonding) tothe distal end of the distal portion 206 of second elongated member 200.In either embodiment, the material composition for the distal valve 210may be the same or different from that of the rest of the secondelongated member 200. In the later case, for example, the distal valve210 may be made of a metallic material while the second elongated member200 is made of a plastic material.

The shape, size, and material composition of various components of thedelivery catheter, including the first elongated member 100, the secondelongated member 200 with the distal valve 210, may be selectedaccording to the need of the application. The first elongated member 100and the second elongated member 200 may be made with flexible materialsif flexibility is required to access the body cavity into which tointroduce the fibers. For example, long, thin, and flexible elongatedmembers may be preferred when the device is to be used for delivery offibers deep inside the body or within the vasculature such as to fill ananeurysm. Short and more rigid elongated members may be used forsub-topical applications such as tissue bulking of the lips or urethralsphincters, for example. Overall, the length of the first elongatedmember 100 and the second elongated member 200 may range from about 1centimeter to any length required to accomplish the goal at hand, forexample, about 3 meters. Illustrative ranges of length of the elongatedmembers 100 and 200 include from about 1 centimeter to about 5centimeters, from about 5 centimeters to about 0.5 meter, from about 0.5meter to about 1 meter, and from about 1 meter to about 3 meters. Thediameter of the first elongated member 100 and the second elongatedmember 200 may range from about 0.001 millimeter to about 20millimeters, again depending on the application at hand. Illustrativeranges of the diameter of the elongated members 100 and 200 includeabout 0.001 millimeter to about 0.01 millimeter, from about 0.01millimeter to about 0.1 millimeter, from about 0.1 millimeter to about 1millimeter, from about 1 millimeter to about 5 millimeters, and fromabout 5 millimeters to about 20 millimeters. The second elongated member200 may also include one or more legs on its periphery to maintain itsposition within the first lumen 120. These legs may be positioned at thedistal end of catheter 200 or along a segment near the distal end.Alternatively, if the material to be delivered in the first lumen 120 issufficiently viscous or the pressure and flow is sufficiently elevatedthe position may be maintained without requiring such peripheralstructures.

As shown in FIG. 2a, elongated members 100 and 200 are connectedtogether by a joint 160 that permits access of at least a portion of thesecond elongated member 200 inside the lumen of the first elongatedmember 100. The joint 160 shown in FIGS. 8a-b includes extension legs162, 164, and 168 and openings 163, 165, and 167. Openings 163 and 165allow access of the lumen of the first elongated member by the secondelongated member 200 and by the fluids flowing into the joint 160 fromlegs 162 and 164. Opening 167 allows connection of the joint 160 withthe rest of the first elongated member 100 and fluid communication withthe distal section 140. A bridge 166 can be included to secure orfortify the connection between the legs and the rest of the firstelongated member 100. The joint 160 as depicted in FIG. 8a has a “Y”shape (with less than 90° angles between legs 162 and 164) while that inFIG. 8b has a “T” shape (with 90° angles between legs 162 and 164).Other shapes may also be adopted.

Referring again to FIG. 2a, the distal valve 210 of the deliverycatheter 12 allows the second lumen 220 to be shut off upon release ofpressure from the injector 180. A shut-off of the second lumen 220results in termination of the feed of the crosslinkable polymer into thedistal section 140. No further crosslinking of the polymer occurs uponthe termination of the feed of the polymerizable agent into the distalsection 140. Diffusion of the crosslinking agent is completely preventedfrom entering the second lumen 220 when the distal valve 210 is closed.

The delivery catheter of the invention allows at least a portion of thesecond elongated member to be slidable within the first lumen 120 of thefirst elongated member 100. To release the crosslinked polymericmaterial formed in and concomitantly to rid it from the distal section140, the second elongated member 200 with the distal valve 210 closedcan be pushed forward towards the distal end 110 of the first elongatedmember 100. The pushing and sliding of the distal valve 210 may cover asmuch as the full length of the distal section 140 or more to assist inclearing the distal section 140 of any formed crosslinked polymer suchas alginate fibers. The distal valve 210 together with the secondelongated member 200 can subsequently be retracted to its originalsetting to resume fiber delivery. Maintenance of pressure and fluid flowin the first lumen 110 can also facilitate removal of the crosslinkedpolymer from the distal section 140 by flushing the fiber out of thedistal section 140. FIGS. 9a-c illustrate as a cartoon the slidingmotion of elongated member 200 within elongated member 100. FIG. 9ashows the second elongated member 200 with the distal valve 210positioned proximally to the distal section 140 and the distal opening110 of the first elongated member 100. FIG. 9b shows the secondelongated member 200 with the distal valve 210 positioned distally tothe distal section 140 and near or at the distal opening 110 of thefirst elongated member 100. FIG. 9c shows the second elongated member200 with the distal valve 210 positioned distally to the distal section140 and distal to the distal opening 110 of the first elongated member100.

The injectors 180 and 280 allow introduction of the crosslinkablepolymeric material and the crosslinking agent into the first and secondlumens. Syringes 180 and 280 may also provide pressure in thecorresponding lumen to facilitate removal of the fiber from the distalsection 140. Depending on the application, any type of injector may beemployed if the desired delivery can be effectively conducted and thedesired pressure exerted.

The delivery catheter may include, instead of or in addition to syringesor injectors, one or more automated pumps. For example, in the deliverysystem 16 shown in FIG. 10a, a first pump 183 may be connected to and influid communication with the first elongated member 100 and the firstlumen 120 through connection port or seal 170 and joint 160. A secondpump 283 may be connected to and in fluid communication with the secondelongated member 200 and lumen 220 through connection port or seal 270of joint 160. Similar to pressure control through injectors, thepressure and material flow in the first and the second lumens 120 and220 may be controlled by the pumps 183 and 283. Reservoirs 196 and 296are connected to pumps 183 and 283 respectively to supply the first andsecond materials to the lumens 120 and 220 of elongated members 100 and200 (FIG. 10b), respectively. Any types of pumps may be used as long asthe purpose of controlling pressure and effecting material delivery isachieved. A pump can be advantageously used with a typical syringe ineffecting a continuous delivery. Such automated syringes or injectorsare well known in the art. Automated and/or computerized control of thepressure and material flow may also be achieved through a control system298 by incorporating appropriate computerized equipment and software.

Referring to FIGS. 11a-c, the delivery catheter can be incorporated intoa gun-like handheld delivery system that allows easy control of deliveryand termination of the polymeric fibers. In addition to featurespreviously described in FIG. 2a, the gun-like delivery system 14includes a handle 190, a trigger or releaser 192 disposed in a chamber193, a panel 194 and a cover 195 for attaching injectors 180 and 280,and mechanisms for effecting an injection upon the pulling or release ofthe trigger or releaser 192. The trigger or releaser 192 mechanicallycontrols the movement of injectors 180 and 280 through mechanisms (suchas levers, gears, ratchet and pawl, and/or motors, not shown). Thesemechanisms are known and within the skill of the trained artisan.

In certain applications, the delivery catheter may include more than twoelongated members to introduce simultaneously more than two separateagents or components into the distal section. Two embodiments of adelivery catheter with three elongated members are shown in FIGS. 12 and13 where each of the delivery catheters 18 and 19 includes elongatedmembers 300, 400, and 500 defining corresponding lumens 320, 420, and520.

In FIG. 12, elongated members 400 and 500 are parallel and side-by-sidewhile each is inside elongated member 300. The remainder of the deliverycatheter 18 is analogous to the delivering catheter shown in FIG. 2aincluding a distal section 340, distal valve 410 and/or distal valve510, joint 360, connection ports or seals 370, 470, and 570, andinjectors 380, 480, and 580. Elongated member 400 with distal valve 410and/or elongated member 500 with distal valve 510 are slidable withinthe first lumen 320 to near or outside of distal opening 310. Thus,clearing of the distal section 340 can be accomplished by either or bothslidable distal valves 410 and 510.

Referring to FIG. 13 in another embodiment, a first elongated member 500is inside a second elongated member 400 that is in turn inside a thirdelongated member 300. The remainder of the delivery catheter 19 isanalogous to the delivery catheter shown in FIG. 2a including lumens320, 420, and 520, distal sections 340 and 440, distal valve 510 and/ordistal valve 410, joints 360 and 460, connection ports or seals 370,470, 476, and 570, and injectors 380, 480, and 580. Elongated member 400with distal valve 410 is slidable within lumen 320 to near or outside ofdistal opening 310. Elongated member 500 with distal valve 510 isslidable within lumen 420 to near or outside of distal opening 410.Thus, clearing of the distal section 340 can be accomplished by slidingdistal valves 410 with the elongated member 400. Clearing of the distalsection 440 can be accomplished by sliding distal valves 510 with theelongated member 500.

Similarly, these or other additional elongated members may be employedfor introduction of additional materials as necessitated by theapplication. For example, additional elongated members may be employedfor introduction of other agents such as bioactive agents. Suchbioactive agents include antibiotics, anti-inflammatory agents,antimicrobials, anti-infective agents, tissue growth promoters,anti-adhesion agents, and bioadhesives. While these materials may bemixed and introduced with either the crosslinking agent or thecrosslinkable polymer, it may be advantageous to introduce themseparately through additional elongated member(s) as described above.For example, the side-by-side arrangement may be well suited forco-delivering of a bioadhesive agent and a homeostatic agent to coat thefiber. The coaxial arrangement may be suited for encapsulation of atherapeutic agent within the fiber, such as an antibiotic agent.

Stabilizing structures (e.g., 250 in FIG. 2a) may be included in thedelivery catheter to stabilize the elongated members. For example, thestabilizer may contain two or more legs peripherally placed between anannular wall of a distal segment of the first elongated member and anannular wall of a distal segment of the second and or additionalelongated member. Stabilizing structures can be used to keep either theopenings and/or the distal segments of the elongated memberssubstantially co-axial or parallel to each other.

The devices and methods of the invention may be used to form polymericfibers such as alginate fibers, or other forms of products, fibrous ornonfibrous.

Besides alginates, any crosslinkable polymers may be employed with acrosslinking agent using the devices and methods of the invention. Othercrosslinkable polymers that may be suitable for use with the deliverycatheter of the invention include both ionically crosslinkable andnon-ionically crosslinkable polymers. To be used in conjunction withthese crosslinkable polymers, crosslinking agents that may be employedinclude both ionic crosslinkers and nonionic crosslinkers, respectfully.

The ionically crosslinkable polymeric material may be anionic orcationic and may include, but are not limited to, at least one polymeror copolymer such as polyacrylic acids, polymethacrylic acid,polyethylene amine, polysaccharides, alginic acid, pectinic acids,carboxy methyl cellulose, hyaluronic acid, heparin, chitosan,carboxymethyl chitosan, carboxymethyl starch, carboxymethyl dextran,heparin sulfate, chondroitin sulfate, cationic starch, and saltsthereof. Illustrative examples of cationic crosslinking ions includepolycations such as calcium, magnesium, barium, strontium, boron,beryllium, aluminium, iron, copper, cobalt, lead, and silver ions.Illustrative examples of anionic crosslinking ions include polyanionssuch as phosphate, citrate, borate, succinate, maleate, adipate andoxalate ions, and, more broadly, anions derived from polybasic organicor inorganic acids. The crosslinker can be a cation or an anion, eithercan be mono- or poly-charged ion. The preferred crosslinking cations arebarium. The preferred crosslinking anions are phosphates.

Non-ionic crosslinking agents may be employed with non-ionicallycrosslinkable polymers. Non-ionic crosslinkers may also be used insteadof or in addition to ionic crosslinkers with ionically crosslinkablepolymer. Thus, a higher crosslinking density and improved mechanicalproperties, i.e., improved stiffness, modulus, yield stress andstrength, may be accomplished by additionally subjecting the ionicallycrosslinkable polymer to non-ionic crosslinking. For example, non-ioniccrosslinking can be accomplished by treatment with a chemicalcrosslinking agent which reacts with groups present in the polymer suchthat covalent bonds are formed connecting different portions of thepolymer or between polymer strands to form a web.

Suitable non-ionic crosslinking agents are polyfunctional compoundspreferably having at least two functional groups reactive with one ormore functional groups present in the polymer. The crosslinking agentcan contain one or more of carboxyl, hydroxy, epoxy, halogen, aminofunctional groups or hydrogen unsaturated groups. Illustrative non-ioniccrosslinking agents include polycarboxylic acids or anhydrides,polyamines, epihalohydrins, diepoxides, dialdehydes, diols, carboxylicacid halides, ketenes and like compounds. Illustrative crosslinkablepolymers include those that possess organic acid functional groups thatare covalently crosslinkable with polyfunctional crosslinking agents.The covalent bonds between the crosslinking agents and the hydrophilicpolymers are susceptible to hydrolysis in the body, releasingwater-soluble components.

One embodiment utilizes crosslinking agents that can form relativelyweak covalent crosslinking bonds, so that these bonds can bede-crosslinked within the body after a desired length of time. Forexample, polymers comprising covalent bonds that are easily hydrolysableat temperature and pH conditions inside the body can serve this purpose.Such polyfunctional covalent crosslinking agents include polyfunctionalaziridines, polyfunctional carbodiimides, polyisocyanate, glutaraldehydeor other polyfunctional crosslinkers wherein the ftnctional groups arecapable of reacting with the organic acid groups, or any activated formsthereof.

Alginate is an inonically crosslinkable polymer. Alginate is aheterogeneous group of linear binary co-polymer of 1-4 linkedβD-mannuronic acid (M) and its C-5 epimer O-L-guluronic acid (G). Themonomers are arranged in blockwise pattern along the polymer chain wheremannuronic blocks (M blocks) and guluronic blocks (G blocks) areinterspaced with sequences containing both M monomers and G monomers(mixed or MG blocks). The proportion and sequential arrangement of theuronic acids in alginate depend upon the species of algae and the kindof algal tissue from which the material is prepared. Commercialalginates are produced from sources including Laminaria hyperborea,Macrocystis pyrifera, Laminaria digitata, Ascophyllum nodosum,Laminariajaponica, Eclonia maxima, Lesonia negrescens and Saragassum sp.

Monovalent cation alginate salts, such as sodium or potassium alginate,are water soluble. Most divalent cations, such as calcium, strontium, orbarium, interact with alginate to form water insoluble but waterpermeable gels. Because of the higher affinity of these divalent cationsfor guluronate compared with mannuronate blocks and because of stericconsiderations, cooperative binding of gelling divalent cations toguluronate within guluronate blocks provides the primary intermolecularcrosslinking responsible for formation of stable alginate gels.Mannuronate and mixed blocks are not crosslinked due to their weakeraffinity for the crosslinking divalent cation, but function as flexibleinterconnecting segments between interacted guluronate blocks.

Different divalent cations have different affinities for mannuronate andguluronate and thus are differentially susceptible to be displaced byexchange with other monovalent or divalent cations. Likewise, dependingon the molecular weight, the number of residues per block and theoverall ratio of guluronate to mixed or mannuronate blocks, differentalginates have different susceptibilities to undergo ion exchangereactions.

The degree of crosslinking, both ionic and non-ionic, can be controlledmainly as a function of the concentration of the crosslinking agent. Thecrosslinking agent may be in a solution of water or of another suitablesolvent or mixture thereof. The solvent is not limited as long as it issuitable for the application. In solution, the concentration of thecrosslinking agent can range from about 0.0001 M to about 10 M and is tobe determined according to the application. In one embodiment, theconcentration of the crosslinking agent ranges from about 0.0001 M toabout 0.001 M. In another embodiment, the concentration of thecrosslinking agent ranges from about 0.001 M to about 0.01 M. In yetanother embodiment, the concentration of the crosslinking agent rangesfrom about 0.01 M to about 0.1 M. In yet another embodiment, theconcentration of the crosslinking agent ranges from about 0.1 M to about1.0 M. In yet another embodiment, the concentration of the crosslinkingagent ranges from about 1.0 M to about 10 M.

Similarly, the crosslinkable polymer such as alginate may be in asolution of water or any solvent suitable for the application. Insolution, the concentration of the crosslinkable polymer can range fromabout 0.0001 M to about 10 M and is to be determined according to theapplication. In one embodiment, the concentration of the crosslinkablepolymer ranges from about 0.0001 M to about 0.001 M. In anotherembodiment, the concentration of the crosslinkable polymer ranges fromabout 0.001 M to about 0.01 M. In yet another embodiment, theconcentration of the crosslinkable polymer ranges from about 0.01 M toabout 0.1 M. In yet another embodiment, the concentration of thecrosslinkable polymer ranges from about 0.1 M to about 1.0 M. In yetanother embodiment, the concentration of the crosslinkable polymerranges from about 1.0 M to about 10 M.

Various additives may be added in the solution of the crosslinkingagent, the solution of alginate, or both. For example, a bioadhesiveagent may be added to the solution of the crosslinking agent and/or thesolution of alginate. Illustrative bioadhesive agents include, but arenot limited to, collagen, laminin, fibronectin, poly-D-lysine,poly-L-lysine, decapeptides. Also, materials that enhance theradiopacity of the fiber may be added to the solution of thecrosslinking agent, the solution of alginate, or both. Illustrativeexamples of radiopaque agents in liquid or solid form include, but arenot limited to, tantalum powder, platinum powder, barium sulfate,bismuth subcarbonate, ionic or non-ionic contrasting agents such asdiatrizoates, iodipamide, iohexol, iopamidol, iothalamate, ioversol,ioxaglate, and metrizamide. Examples of liquid contrasting agentsinclude Omnipaque®, Visipaque® manufactured by Nycomed Amersham Imagingof Princeton, New Jersey, or RenoCal® manufactured by Bracco DiagnosticInc. of Princeton, N.J. Other natural or synthetic additives that may beadded include, but are not limited to, anti-inflammatory agents,antimicrobials such as antibiotics or antifungal agents, anti-viralagents, anti-infective agents, tissue growth promoters,immunosuppressants, and anti-adhesion agents.

In another aspect, the invention relates to methods for delivering anextrudable material within the body of a mammal. In one embodiment, themethod includes the following steps. A delivery catheter as describedabove is provided to deliver a first and second materials into a body. Afibrous material is extruded out of the distal section and into the bodyof a mammal. In one embodiment, the extrusion step includes deliveringthrough the first lumen to the distal section a first material having acrosslinking agent and delivering through the second lumen to the distalsection a second material having a crosslinkable polymer.

To deliver a fiber into the body of a mammal, the distal segment of adelivery catheter is inserted into a body of a patient eitherpercutaneously or by entry into an existing orifice or duct. Access intothe body may be direct or with the help of trocars, stylets, needles,cannulas, dilators, endoscopes or the like. A first material containinga crosslinking agent and a second material containing a crosslinkablepolymer are introduced into the distal section through the first lumenand the second lumen, respectively.

In one embodiment of the invention, as the first material and the secondmaterial are introduced into the mixing chamber, the first materialsurrounds the second material. The contacting of the first and thesecond materials results in the formation of crosslinked polymericmaterial inside the distal section and formation of a fibrous structure.The sustained delivering of the first and second materials to the distalsection creates a continuously growing fiber of crosslinked polymericmaterial. The formation of the fiber may be terminated by terminatingthe feed of either or both the first and second materials. The methodmay further include a step of cutting the fiber so formed. The fiber maybe cut by the termination of the feed of one or both of the first andsecond materials into the distal section, or additionally, by an actionof the valve walls which operate as blades and the closing of whichoperates as a transversal slicing of the fiber.

To facilitate the exiting of the terminated fibers from the distalsection, the fibers may be pushed out of the distal section by slidingdistally the second elongated member and/or by maintaining pressure orflow of the crosslinking agent solution in the first lumen. The deliverycatheter allows the second elongated member to penetrate into the distalsection thereby pushing the formed fibers out of the distal section.Thereafter, the formation and termination process can be repeated asneeded by repeating the sequence of steps described herein above.

Referring to FIGS. 14a-b, fibers 20 such as alginate fibers are formedinside the distal section 140 as the crosslinking agent and the alginatesolution are introduced into the distal section 140 through the firstlumen 120 and the second lumen 220, respectively. The distal section 210and the second elongated member 200 can be slid toward the distalopening 110 (FIG. 14b). Such sliding results in alginate fibers 20 beingpushed out of the distal section 140. Referring to FIGS. 9a-c again, thesecond lumen 200 with the distal valve 210 can be slid to a positionsuch that the distal valve 210 is distal to the distal opening 110.

In one embodiment of the invention, the first material is a solutioncontaining a crosslinking agent. The second material is a solutioncontaining a crosslinkable polymer. As the crosslinking agent and thealginate enter the distal section, the crosslinking agent solutionsurrounds the crosslinkable polymer solution. In another embodiment, thefirst material is a solution containing a crosslinkable polymer. Thesecond material is a solution containing a crosslinking agent. As thecrosslinking agent and the crosslinkable polymer enter the distalsection, the crosslinkable polymer solution surrounds the crosslinkingagent solution.

The devices and methods of the present invention may be used for anytreatment, including urological and neurological procedures, involvingthe introduction of a filler into the body by mixing two or more agentsin the body of a mammal. In certain applications, the crosslinkedpolymeric material may be formed and used outside the body of a mammal.

EXAMPLE 1

A solution (Solution 1) of a crosslinking agent (calcium chloride, 0.5wt. % to 5.0 wt. %) and a bioadhesive agent (polyethylene oxide, 0.5 wt.% to 5.0 wt. %) is placed in a syringe (Syringe 1). A solution (Solution2) of a commercially available alginate (sold by Pronova of Oslo,Sweden, sodium alginate, 0.5 wt. % to 5.0 wt. %) is placed in a secondsyringe (Syringe 2). The concentrations of the reagents in Syringes 1and 2 may be varied to increase or decrease the crosslinking rate of thealginate. Syringes 1 and 2 are then connected to the “Y” shaped joint ofthe fiber delivery catheter. Solutions 1 and 2 are then injected intothe distal section of the first lumen wherein an alginate fiber forms ata rate that depends on the concentrations of solution 1 and 2. A typicalrate of fiber formation may be 0.2 mL/min. This rate can be varied withchanging the crosslinking agent to alginate ratio. The rate ofcrosslinking is also affected by the use of additives such as radiopaquefillers as well as other additives such as listed above in

The pressure from Syringe 2 is released, resulting in the closing of thedistal valve and the termination of the delivery of Solution 2 into thedistal section. At the same time, the closing of the distal valve cutsthe alginate fiber already formed. Pushing of the second elongatedmember by pushing Syringe 2 forwards removes the alginate fiber out ofthe distal section. Syringe 2 is then withdrawn back to its originallocation and alginate fiber formation can be resumed by actuation of theplungers in Syringes 1 and 2, opening the distal valve, and injection ofSolutions 1 and 2 into the distal section.

Variations, modifications, and other implementations of what isdescribed herein will occur to those of ordinary skill without departingfrom the spirit and the scope of the invention. Accordingly, theinvention is not to be defined or limited only by the precedingillustrative description.

What is claimed is:
 1. A delivery catheter, comprising: (a) a firstelongated member defining a first distal opening and a first lumenextending within the first elongated member, the first elongated memberfor delivering a first material through the first lumen and into adistal section of the first lumen near the first distal opening; (b) asecond elongated member comprising a distal valve and a second lumenextending within the second elongated member, the second elongatedmember for delivering a second material through the second lumen and thedistal valve, at least a portion of the second elongated member beingslidably disposed within at least a portion of the first lumen such thatthe distal valve is selectively slidable (i) to allow delivery of thesecond material through the second lumen and the distal valve and intothe distal section, and (iv) to push at least some of the first andsecond materials from the distal section and out of the first distalopening; (c) a first injector adapted for connection to the firstelongated member for injecting the first material into the first lumen;and (d) a second injector adapted for connection to the second elongatedmember for injecting the second material into the second lumen.
 2. Thecatheter of claim 1 wherein the distal valve comprises a one-wayflow-control valve.
 3. The catheter of claim 2 wherein the one-wayflow-control valve comprises a slit that opens and closes upon pressuredifferentiation between the second lumen and the distal section toregulate delivery of the second material into the distal section.
 4. Thecatheter of claim 3 wherein the slit opens to a size of about 0.00001mm² to about 100 mm².
 5. The catheter of claim 1 wherein one of thefirst and second lumens has a diameter of about 0.001 mm to about 20 mm.6. The catheter of claim 1 wherein said first injector comprises a firstpump connected to the first elongated member for delivering the firstmaterial into the first lumen; and wherein said second injectorcomprises a second pump connected to the second elongated member fordelivering the second material into the second lumen.
 7. The catheter ofclaim 6 wherein each of the first and second pumps comprises a syringe.8. The catheter of claim 1 wherein the first elongated member furtherdefines a first proximal port, and the second elongated member furtherdefines a second proximal port.
 9. The catheter of claim 8 furthercomprising an access joint between a first proximal joint and the firstdistal opening, the access joint allowing insertion of the at least aportion of the second elongated member into the at least a portion ofthe first lumen.
 10. The catheter of claim 9 wherein the access joint isY-shaped.
 11. The catheter of claim 9 wherein the access joint isT-shaped.
 12. The catheter of claim 1 further comprising a stabilizer tokeep the second elongated member substantially co-axial with the firstelongated member.
 13. The catheter of claim 12 wherein the stabilizercomprises two or more legs peripherally placed between an annular wallof a distal segment of the first elongated member and an annular wall ofa distal segment of the second elongated member.
 14. The catheter ofclaim 1 wherein the selectively slidable distal valve is alternativelypositionable outside the first lumen and outside the first distalopening.
 15. The catheter of claim 1 wherein at least one of the firstand second elongated members has a length from about 1 cm to 3 m.
 16. Adelivery catheter, comprising: (a) a first elongated member defining afirst distal opening and a first lumen extending within the firstelongated member, the first elongated member for delivering a firstmaterial through the first lumen and into a distal section of the firstlumen near the first distal opening; (b) a second elongated membercomprising a distal valve and a second lumen extending within the secondelongated member, the second elongated member for delivering a secondmaterial through the second lumen and the distal valve, at least aportion of the second elongated member being slidably disposed within atleast a portion of the first lumen such that the distal valve isselectively slidable (i) to allow delivery of the second materialthrough the second lumen and the distal valve and into the distalsection, and (ii) to push at least some of the first and secondmaterials from the distal section and out of the first distal opening;(c) a first pump connected to the first elongated member for deliveringthe first material into the first lumen; and (d) a second pump connectedto the second elongated member for delivering the second material intothe second lumen.
 17. The catheter of claim 16 wherein each of the firstand second pumps comprises a syringe.
 18. A delivery catheter,comprising: (a) a first elongated member defining a first distalopening, a first proximal port and a first lumen extending within thefirst elongated member, the first elongated member for delivering afirst material through the first lumen and into a distal section of thefirst lumen near the first distal opening; (b) a second elongated membercomprising a distal vave and a second lumen extending within the secondelongated member, the second elongated member defining a second proximalport and for delivering a second material through the second lumen andthe distal valve, at least a portion of the second elongated memberbeing slidably disposed within at least a portion of the first lumensuch that the distal valve is selectively slidable (i) to allow deliveryof the second material through the second lumen and the distal valve andinto the distal section, and (ii) to push at least some of the first andsecond materials from the distal section and out of the first distalopening; and (c) an access joint between a first proximal joint and thefirst distal opening, the access joint allowing insertion of the atleast a portion of the second elongated member into the at least aportion of the first lumen.
 19. The catheter of claim 18 wherein theaccess joint is Y-shaped.
 20. The catheter of claim 18 wherein theaccess joint is T-shaped.
 21. A delivery catheter, comprising: (a) afirst elongated member defining a first distal opening, a first proximalport and a first lumen extending within the first elongated member, thefirst elongated member for delivering a first material through the firstlumen and into a distal section of the first lumen near the first distalopening; (b) a second elongated member comprising a distal valve and asecond lumen extending within the second elongated member, the secondelongated member defining a second proximal port and for delivering asecond material through the second lumen and the distal valve, at leasta portion of the second elongated member being slidably disposed withinat least a portion of the first lumen such that the distal valve isselectively slidable (i) to allow delivery of the second materialthrough the second lumen and the distal valve and into the distalsection, and (ii) to push at least some of the first and secondmaterials from the distal section and out of the first distal opening;and (c) a stabilizer to keep the second elongated member substantiallyco-axial with the first elongated member.
 22. The catheter of claim 21wherein the stabilizer comprises two or more legs peripherally placedbetween an annular wall of a distal segment of the first elongatedmember and an annular wall of a distal segment of the second elongatedmember.